At the end of 1987, after the isolation between the two sides of the strait was broken for more than 30 years, personnel exchanges and economic and cultural exchanges between the two sides of the strait developed, and at the same time, various problems arose. In order to solve these problems, Taiwan Province Province had to adjust the "three noes" policy of "no contact, no compromise and no negotiation" and set up a government-authorized non-governmental intermediary agency to contact and negotiate with the mainland on June 5438+0990165438+1October 2 1 to deal with the government. In order to facilitate contact and discussion with SEF, the Taiwan Affairs Office of the Central Committee and the Taiwan Affairs Office of the State Council promoted the establishment of the Association for Relations across the Taiwan Strait on June 5, 2006+099165438+February 616, and authorized the adherence to the one-China principle as the basis for exchanges and discussions between the two associations.
1992 10 During the talks from 28th to 30th, NPC and CPPCC discussed how to express their adherence to the one-China principle in the cross-strait transactional talks. The basic attitude of ARATS is that specific issues in cross-strait exchanges are China's internal affairs and should be resolved through consultation on the basis of the one-China principle. In business negotiations, as long as we show our basic attitude of adhering to the one-China principle, we can avoid the political meaning of the one-China, and the expression can be fully negotiated.
During the talks in Hong Kong, ARATS put forward five written opinions, and SEF of Taiwan Province Province also put forward five written opinions according to the conclusion of the National Unification Council. Although Taiwan Province also agrees that the use of notarial certificates between the two sides of the strait is an internal affair of China, and both sides should adhere to the one-China principle and express their desire for national reunification, it is difficult for the two associations to reach an agreement on a written expression plan. At the end of the talks, SEF representatives added three more expressions and reached the final expression: "In the process of seeking national reunification, both sides of the Taiwan Strait adhere to the principle of one China, but they have different understandings of the meaning of one China. However, in view of the increasingly frequent cross-strait non-governmental exchanges, in order to protect the rights and interests of people on both sides of the strait, the issue of document verification should be properly resolved. " It is also suggested that "the one-China principle should be expressed by their respective oral statements". The representative of ARATS said that this is the main achievement of the talks and will give a formal reply after SEF's suggestions and specific expressions are reported.
Shortly after the Hong Kong talks ended, ARATS officially wrote to SEF, Taiwan Province Province, on June 6, 1992+ 1, saying: "In this working meeting, the representatives of your association suggested that the one-China principle should be expressed by the oral statement of the two associations on the premise of mutual understanding, and put forward specific expression contents, clearly indicating that both sides of the Taiwan Strait adhere to the one-China principle. I will fully respect and accept your suggestion. " Now I'll write you the main points of my oral statement: both sides of the Taiwan Province Strait adhere to the one-China principle and strive for national reunification. However, the political meaning of "One China" is not involved in cross-strait business talks. In this spirit, the use of cross-strait notarial certificates (or other negotiation matters) will be properly resolved. "After the ARATS letter, SEF finally provided a demonstration plan. On February 3, 65438, SEF wrote back to ARATS, saying that it had no objection to reaching an understanding. At this point, the discussion on the expression of one China principle has come to an end, and two concrete expressions acceptable to both sides have been formed.
It can be clearly seen from the process and contents of the above-mentioned talks and correspondence that in 1992, the two sides did reach an understanding that "both sides of the strait adhere to the one-China principle", but the political connotation of one China has never been discussed. Since there is no discussion, there is no knowledge of "separate statements". It is on this basis that the two sides of the strait have properly handled cross-strait affairs involving people's rights and interests. In 1993, they held the "Wang Koo Talks" in Singapore, signed a series of agreements on cross-strait exchanges and cooperation, and the cross-strait political dialogue was also put on the agenda.
Antofloxacin Hydrochloride Antofloxacin Hydrochloride is the first fluoroquinolone new drug independently created by scientists in China, and it is an important achievement made by the China Academy of Sciences in implementing the knowledge innovation project and the national major scientific and technological project of "major new drug creation". The successful development of the drug will produce remarkable economic and social benefits, and at the same time, it will further enhance and promote the research and development of innovative drugs with independent intellectual property rights in China, and accelerate the improvement of China's independent drug innovation capability.
Fluoroquinolones (ofloxacin) are one of the three main antibacterial drugs in China at present, with a market scale of about 654.38+000 billion yuan, which has played an important role in safeguarding the health of our people. Our country began to imitate the first generation drug nalidixic acid from 1967, but for more than 40 years, our country has not developed this kind of new drug independently. At present, more than 20 old varieties of ofloxacin used in clinic have some defects such as weak antibacterial activity, poor metabolic characteristics or large side effects, so it is urgent to replace new products.
After more than ten years, scientists from Shanghai Institute of Pharmacology, China Academy of Sciences independently developed the first national first-class fluoroquinolone antibacterial drug-Antofloxacin Hydrochloride (patent number ZL97 106728.7). From 65438 to 0997, Shanghai Institute of Pharmacy applied for the patent of Antofloxacin Hydrochloride and its series of compounds, and in 2000, it was granted the patent rights of compounds, synthetic process and antibacterial use authorized by China Patent Office. In April 65438+May, 2009, it obtained the new drug certificate issued by the State Food and Drug Administration of the United States, and will be listed soon.
Antofloxacin hydrochloride is also a successful example of joint development of innovative drugs by domestic scientific research institutes and enterprises. 200 1, Anhui Global Pharmaceutical Co., Ltd. accepted the patent transfer of Antofloxacin, carried out the first, second and third phase clinical research, and the combination of production and research accelerated the research and development of this product.
Relying on the construction of national and China Academy of Sciences' drug innovation system, scientists from Shanghai Institute of Pharmacology, China Academy of Sciences, from 1993, have conducted in-depth and systematic research on the synthesis methodology, structure-activity relationship and drug properties of fluoroquinolones. Supported by the National Special Program for New Drug Creation, the "863" Program, the National Natural Science Foundation and the Knowledge Innovation Project of the Chinese Academy of Sciences, researcher Yang Yushe, academician Ji Ruyun and their team adopted the strategy of structural optimization, devoted themselves to studying the gene structure-pharmacodynamic relationship, structure-metabolic characteristics relationship and structure-toxicity relationship of levofloxacin, synthesized a series of new compounds, and finally screened out a fluoroquinolone antibacterial drug with a new chemical structure-American National Hydrochloride. In August, 2008, when the drug was declared as a major scientific and technological project of "major new drug creation", it was highly recognized by the evaluation experts and ranked first among new chemical drugs.
Compared with existing drugs, antofloxacin hydrochloride has obvious advantages in safety and efficacy, especially in drug metabolism characteristics. Gram-positive bacteria and gram-negative bacteria, including methicillin-resistant Staphylococcus aureus (MRSA) and Staphylococcus epidermidis (MRSE), were isolated from 1080, showing strong antibacterial and bactericidal activities. Antofloxacin hydrochloride can kill more than 99% of bacteria by interacting with bacteria for 2 ~ 4 hours. No matter oral administration, subcutaneous administration or intravenous administration, it has a strong protective effect on mice infected with Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Streptococcus pneumoniae and Klebsiella pneumoniae in abdominal cavity, and its curative effect is better than that of existing fluoroquinolones, such as ofloxacin and ciprofloxacin. Antofloxacin hydrochloride has good safety. Among the important indicators of the safety of quinolones-phototoxicity, its toxicity is obviously lower than the existing main products, such as Lomefloxacin, Sparfloxacin, fleroxacin and ciprofloxacin, and it is similar to norfloxacin, which has almost no phototoxicity. Inhibition of HERG potassium channel may lead to prolonged QT interval of ECG, which is the most worrying side effect of fluoroquinolones. The inhibitory activity of Antofloxacin Hydrochloride on HERG potassium channel current IKr is 10.5 times weaker than levofloxacin, which is the safest in clinic, and 172 times weaker than sparfloxacin, which makes this product have a high safety range. Compared with the fourth-generation fluoroquinolones listed in recent years, such as Prifloxacin, gemmoxifloxacin and moxifloxacin, Antofloxacin hydrochloride has the advantages of low manufacturing cost and environmental friendliness, and it is a good new drug that China people can afford.
Recently, Antofloxacin Hydrochloride and its tablets, a national first-class drug jointly developed by Shanghai Institute of Pharmacology of China Academy of Sciences and Anhui Qiu Huan Pharmaceutical Co., Ltd., obtained the new drug certificate and drug approval number issued by SFDA.
Antofloxacin hydrochloride is the first innovative quinolone drug with independent intellectual property rights (patent number: ZL97 106728.7) developed by Shanghai Institute of Drugs for more than ten years. Antofloxacin hydrochloride is a new antibacterial drug, which has the characteristics of long biological half-life, broad antibacterial spectrum, strong antibacterial activity, wide tissue distribution, good absorption, high bioavailability, good safety and little toxic and side effects, and its comprehensive performance is better than that of similar drugs on the market at present. The medicine has obvious curative effect on treating skin system, respiratory system and urinary system infections.
In June 2004, SFDA approved Antofloxacin Hydrochloride and its tablets for clinical study of new drugs, and completed the first phase of clinical study. In June 2006, after the second and third clinical studies were completed, Antofloxacin Hydrochloride and its tablets applied to SFDA for new drug certificate and drug approval number.
Phase I clinical studies have proved that antofloxacin hydrochloride has good drug metabolism characteristics. Compared with the latest fourth-generation fluoroquinolones, the oral dosage is the lowest, the protein binding rate is the lowest, and the longest half-life is 20 hours, and it only needs to be taken 1 time every day. It is a real long-acting fluoroquinolone antibacterial drug.
Phase II/III clinical trials (involving 943 patients) proved that Antofloxacin Hydrochloride was effective in treating bacterial infectious diseases of respiratory tract, urinary tract and skin and soft tissue, with few adverse reactions, and the total effective rate was over 95%. For the same course of treatment and the same curative effect, the total dose of this product is only 1600 mg, which is less than the total dose of levofloxacin of 2,800 mg 1200 mg, showing higher curative effect and higher safety.
Antofloxacin hydrochloride is the first fluoroquinolone new drug independently created by scientists in China, and it is an important achievement made by the China Academy of Sciences in implementing the knowledge innovation project and the national major scientific and technological project of "major new drug creation". The successful development of the drug will produce remarkable economic and social benefits, and at the same time, it will further enhance and promote the research and development of innovative drugs with independent intellectual property rights in China, and accelerate the improvement of China's independent drug innovation capability.